The hypothesis being tested is that psoriasis is a disease mediated by activated (CD25+) T-lymphocytes and that blockage of the IL-2 receptor alpha-subunit (CD25 moiety) decreases IL-2 mediated signaling and thereby improves psoriasis. Based on the information at hand, this hypothesis must be considered in two different contexts with respect to a clinical trial design. The first test of this hypothesis is through administration of humanized anti-TAC antibodies to patients with active psoriasis vulgaris. In this mode, we hypothesize that CD25 blockage would prevent high-affinity IL-2 receptor interaction and that on-going proliferation of disease-mediating T-cell clones would be blocked or decreased. Hence, generation of new effector lymphocytes would be blocked. Accordingly, with ongoing depletion of effector lymphocytes, there would eventually be a loss of disease-producing effector T-lymphocytes. Potentially, CD25 blockade in existing effector lymphocytes could affect their function, but existing data on cytokine production suggests that some effector functions could still be enabled. According to this model, maximal disease improvemtne would be produced only by complete CD25 blockade for a sufficiently long period to permit eradication of pre-formed effectors (postulated to be CD8+CTLs). The second test of this hypothesis is in the setting where effector T-cells have been inactivated or eradicated by other means. The first example is after ultraviolet B phototherapy when CD25 blockade would be used to prevent clonal expansion of new disease-mediating effector T-cells. This setting may have less stringent requirements for actions of humanized anti-TAC, as the starting point of drug administration is before CD25 is up-regulated on activated T-cells and before high concentrations of IL-2 are released from activated T-cells. In this mode, there would be no requirement that effector functions are directly inhibited by CD25 blockade, only that generation of new effectores would be prevented. This setting is approximately equivalent to the established use of humanized anti-Tac in prevention of renal allograft rejection (antibodies are administered before initiation of the immune response to the allograft). In in vitro experiments, blockade of CD25 during the initiation of T-cell activation (to mitogens) inhibits proliferation more effectively than blockade of CD25 24-48h after initiation of activation (unpublished data). The second instance would be to administer this agent after cyclosporine-induced clearing. Cyclosporine acts to prevent transcription of IL-2 gene, which may or may not decrease the overall number of T-cells in tissue. It is also our experience that T-cells decrease in psoriatic lesions after therapeutic doses of cyclosporine. This decrease in not related to increased apoptosis, but probably that these T-cells are redistributed. If CD25 blockade is given after cyclosporine, it may be successful in preventing clonal expansion and local recruitment, since the mitogenic stimulus will have previously been down-regulated.